Public Release: 23-Sep-2008
Also in the Sept. 23 JNCI

The breast cancer incidence in China is predicted to climb from the current rate of 10 cases per 100,000 women aged 55 years to more than 100 cases per 100,000 women in 2021.

The current incidence of breast cancer in China is low compared with the rate in Western countries. But as more Chinese women adopt a Western life style, the rate is expected to climb.

To estimate the breast cancer incidence in China in coming years, Eleni Linos, M.D., previously of the Harvard School of Public Health in Boston and now of Stanford University Hospital in Palo Alto, Calif., and colleagues adapted an existing breast cancer model for use in China. They calibrated the Rosner-Colditz log incidence breast cancer model, which was developed to estimate incidence in white U.S. women, to the Chinese population using data from the Shanghai Women's Health Study cohort of 74,942 women. The researchers then applied the model to estimate the incidence of breast cancer in 17,078 women aged 35 years in 2001 who participated in the Chinese National Family Planning and Reproductive Survey. They extrapolated from those data to the entire Chinese population.

In addition to predicting the increase in breast cancer incidence for women aged 55 years, the researchers estimated that there will be a total of 2.5 million cases of breast cancer by 2012 in Chinese women who were 35 years of age in 2001. Alterations in lifestyle, such as reduced alcohol consumption and hormone use, and less weight gain could theoretically prevent 270,000 of those cases.

"These results point to an emerging epi¬demic of breast cancer in China, where breast cancer incidence rates are approaching those in Western nations, in which breast cancer is the most commonly diagnosed female cancer," the authors write. "Our findings raise impor¬tant issues regarding future health care infrastructure needs, the role of breast cancer screening programs, and possible prevention strategies."

In an accompanying editorial, Regina Ziegler, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues compared the authors' predicted incidence rates using the Rosner-Colditz model to the incidence rates projected by extrapolating from observed rates in Chinese women, aged 35, living in urban Shanghai and rural Qidong County. "The excellent agreement between the model-based and empirical extrapolation approaches gives us confidence that breast cancer incidence in China will increase to roughly 85 per 100 000 woman-years by 2021 if current trends continue," the editorialists write.

The impact on breast cancer incidence of modifying lifestyle and reproductive risk factors, including those related to family planning, is less certain, however, because the results of interventions are hard to predict. Moreover, the Rosner-Colditz model could be calibrated more accurately if data on risk factor prevalence and breast cancer incidence were available from all of China, including both rural and urban communities. Collecting more comprehensive survey data for China could not only improve projections of breast cancer incidence but also guide future health policies.

Childhood Cancer Survivors Continue To Have Higher Mortality Rates than the General Population

Survivors of childhood or adolescent cancer have a greater than 8-fold increased risk of death than the general U.S. population 16 to 32 years after hitting the five-year survival mark.

The proportion of childhood and adolescent cancer patients who survive five years after their diagnosis has been growing over the last four decades. However, past studies indicated that these individuals continue to have excess morbidity and mortality due to their original disease and treatments.

To find out what the long-term risk of death is for these individuals, Ann Mertens, Ph.D., of Emory University and Children's Healthcare of Atlanta and colleagues examined data from 20,483 five-year survivors who were diagnosed with childhood or adolescent cancer between January 1, 1970 and December 31, 1986 and enrolled in the Childhood Cancer Survivor Study. The researchers searched the National Death Index and state death records for deaths occurring between January 1, 1976 and December 31, 2002. With that information, they calculated cause-specific mortality rates and the overall ratio of observed deaths relative to the number of expected deaths in the general population, which is called the standardized mortality ratio.

During the follow-up period, 2,821 (13.8%) of the five-year survivors died. The overall standardized mortality ratio was 8.4 and the absolute excess risk of death from any cause was 7.36 deaths per 1,000 person-years. Of the 2,534 individuals whose cause of death could be identified, 57.5% died due to disease recurrence. When compared with what would be expected in a population of this age group, substantial increases in deaths due to subsequent malignancy, heart disease, and pulmonary problems were found.

"In conclusion, children and adolescents diagnosed with cancer continue to be at elevated risk for death due to recurrences of the primary disease, and as a result of late effects of therapy," the authors write.

The internal region of tumors often lacks oxygen and is less responsive to some therapies. To attack that hypoxic core, researchers have tried injecting tumor-bearing mice with anaerobic bacteria, such as Cp, that thrive in oxygen-depleted environments. However, wild-type Cp retains the ability to grow in the presence of oxygen and led to toxic effects in other tissues making it unsuitable for anti-cancer therapy.

In the current study, Savio Woo, Ph.D., of the Mount Sinai School of Medicine in New York and colleagues deleted a key oxygen tolerance gene (sod) from the bacterial genome. They also introduced a gene, PVL, from the bacterium Staphylococcus aureus that evades inflammatory responses in the host. They tested the anti-tumor activity of the Cp/sod-/PVL bacteria by injecting it intravenously into mice that had pancreatic tumors.

Mice injected with Cp/sod- bacteria had fewer toxic effects than those injected with wild-type Cp. Moreover, mice treated with the Cp/sod-/PVL bacteria had fewer inflammatory cells in the tumor site than those injected with either the wild-type or Cp/sod- bacteria. The median tumor-free survival for animals injected with the Cp/sod-/PVL bacteria was 77 days--and approximately half of the animals became long-term survivors--compared with 30 days and no long-term survivors for those treated with the Cp/sod- bacteria.

"Taken together, this newly constructed bacterial strain, Cp/sod-/PVL, has substantially elevated tumor selectivity and onco¬pathic potency. These improvements may lead to the development of safe and effective oncopathic agents for the treatment of patients with pancreatic cancer and other poorly vascularized tumors in the future," the authors conclude.

Biomarker Test May Be Useful for Detection of Bladder Cancer Cells in Urine

The use of fluorescence in situ hybridization (FISH) to determine the number of copies of the Aurora kinase A (AURKA) gene in urothelial cells isolated from urine is a possible biomarker test for the detection of bladder cancer.

Aurora kinase A is a key regulator of chromosome segregation during cell division. Overexpression of this protein is common in cancers, including bladder cancer, and leads to missegregation of chromosomes and aneuploidy.

In the current study, Bogdan Czerniak, M.D., Ph.D., of the University of Texas M. D. Anderson Cancer Center in Houston and colleagues overexpressed Aurora kinase A in urothelial cells in vitro and then measured chromosome copy number. The team examined the expression level of AURKA in patient biopsy samples. They also used FISH to examine the number of AURKA gene copies in cells isolated from the urine of 23 bladder cancer patients and 7 healthy control subjects to devise a biomarker test for bladder cancer detection. The biomarker test was validated on an independent group of 100 bladder cancer patients and 148 control subjects.

Forced overexpression of the AURKA gene induced aneuploidy and genomic instability in urothelial cells in vitro. The protein was overexpressed naturally in patient tumor samples. Using the FISH test for the AURKA gene, the researchers were able to accurately identify 87% of the bladder cancer patients and correctly categorize the control subjects as not having bladder cancer 96.6% of the time.

"Our findings suggest that the AURKA FISH test may be more effective than cytology in detecting bladder cancer," the authors write.

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